Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions

Br J Anaesth. 2017 Nov 1;119(5):908-917. doi: 10.1093/bja/aex260.


Background: Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented.

Methods: Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3-4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines.

Results: Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79-1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines.

Conclusions: An etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine.

Clinical trial registration: NCT01637220.

Keywords: anaesthesia; anaphylaxis; cardiac output; general; hypocapnia; neuromuscular blocking agents.

Publication types

  • Multicenter Study

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anesthesia / adverse effects*
  • Biomarkers / metabolism
  • Carbon Dioxide / metabolism*
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / metabolism
  • Female
  • Humans
  • Intraoperative Complications / diagnosis*
  • Intraoperative Complications / metabolism
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Severity of Illness Index
  • Young Adult


  • Biomarkers
  • Carbon Dioxide

Associated data

  • ClinicalTrials.gov/NCT01637220